Patients with obstructive sleep apnea (OSA) experience nocturnal oscillations of systemic and pulmonary artery pressure, with marked elevations of pressure at apnea termination. Over time, these abrupt elevations may contribute to chronic cardiovascular disease and even sudden death, but the causes and acute consequences of these oscillations remain uncertain. While the hemodynamic fluctuations have been attributed to hypoxemia, resumption of ventilation, or sudden changes in intrathoracic pressure, our preliminary data suggest an alternative explanation. We hypothesize that arousal may be primarily responsible for the acute cardiovascular response to sleep related upper airway obstruction. Our studies in patients and normals indicate that arousal from sleep produces marked increases in peripheral vascular tone, but decreases in ejection fraction and cardiac output. In addition, based on our studies, we hypothesize that the hemodynamic oscillations may acutely contribute to the development of further episodes of obstruction, promote diurnal hypertension, and predispose to coronary and cerebral ischemia. To test the first hypothesis, we will further define the cardiovascular response to arousal using continuous measurements of left ventricular volume (nuclear VEST) and arterial pressure. In normal sleeping volunteers we will use respiratory and nonrespiratory stimuli to produce arousal and we will assess whether circulatory reflexes might modify the hemodynamic response to arousal. Next, in patients with OSA, we will investigate the contribution of arousal, independent of hypoxemia, intrathoracic pressure swings, and resumption of ventilation to the marked decreases in ejection fraction and cardiac output that occur at apnea termination. Finally, we will examine the response of the pulmonary circulation to arousal independent of hypoxemia. In the second phase of the project, we will use neck suction and pharmacologic methods to assess the ability of baroreceptor stimulation to alter upper airway muscle activity. We will use the same techniques to determine whether nocturnal oscillations in blood pressure can produce baroreceptor resetting overnight. And we will examine the potential for cardiac and cerebral ischemia during sleep in susceptible patients with OSA. We hope these studies will provide greater understanding of the morbid cardiovascular consequences of this disease.